Official reprint from UpToDate®

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Clinical presentation, diagnosis, and staging of colorectal

cancer
Authors: Finlay A Macrae, MD, Johanna Bendell, MD
Section Editor: Kenneth K Tanabe, MD
Deputy Editors: Diane MF Savarese, MD, Shilpa Grover, MD, MPH, AGAF

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: May 2019. | This topic last updated: Oct 22, 2018.

INTRODUCTION

Colorectal cancer (CRC) is a common and lethal disease. It is estimated that approximately
145,600 new cases of large bowel cancer are diagnosed annually in the United States [1],
including approximately 101,420 colon and 44,180 rectal cancers. Approximately 51,020
Americans are expected to die of large bowel cancer each year. Although CRC mortality has been
progressively declining since 1990, at a current rate of approximately 1.7 to 1.9 percent per year
[2], it still remains the third most common cause of cancer death in the United States in women,
and the second leading cause of death in men. Global, country-specific incidence and mortality
rates are available from the World Health Organization GLOBOCAN database.

In contrast to these declines, the incidence of CRC in men and women under the age of 50 has
been steadily increasing at a rate of 2.1 percent per year from 1992 through 2012 [3]. These
increases are driven predominantly by left-sided cancers in general and rectal cancer in particular
(3.9 percent per year) [4]. Current literature suggests that over 86 percent of those diagnosed
under the age of 50 are symptomatic at diagnosis, and this is associated with more advanced
stage at diagnosis and poorer outcomes [5]. At present, screening is not recommended for
individuals under the age of 50 unless they have inflammatory bowel disease, a history of
abdominal radiation, a positive family history, or a predisposing inherited syndrome. (See
"Screening for colorectal cancer: Strategies in patients at average risk" and "Screening for
colorectal cancer in patients with a family history of colorectal cancer or advanced polyp" and
"Colorectal cancer: Epidemiology, risk factors, and protective factors", section on 'Incidence' and
"Surveillance and management of dysplasia in patients with inflammatory bowel disease".)

CRC is diagnosed after the onset of symptoms, or through screening colonoscopy or fecal occult
blood testing in the majority of patients. Screening of asymptomatic individuals for CRC is
advocated by major societies and preventive care organizations. Screening has been shown to
detect asymptomatic early-stage malignancy and improve mortality. However, while compliance
with CRC screening guidelines is steadily improving, it is still relatively low. (See "Screening for
colorectal cancer: Strategies in patients at average risk".)

The clinical presentation, diagnosis, and staging of CRC will be reviewed here. The pathology,
prognostic determinants, and treatment of colon and rectal cancer are discussed elsewhere.

● (See "Pathology and prognostic determinants of colorectal cancer".)

● (See "Overview of the management of primary colon cancer".)
● (See "Surgical resection of primary colon cancer".)
● (See "Adjuvant therapy for resected stage III (node-positive) colon cancer".)
● (See "Adjuvant chemotherapy for resected stage II colon cancer".)
● (See "Adjuvant therapy for resected colon cancer in elderly patients".)
● (See "Rectal cancer: Surgical techniques".)
● (See "Neoadjuvant chemoradiotherapy, radiotherapy, and chemotherapy for rectal
adenocarcinoma".)
● (See "Adjuvant therapy for resected rectal adenocarcinoma in patients not receiving
neoadjuvant therapy".)

CLINICAL PRESENTATION

Patients with colorectal cancer (CRC) may present in three ways:

● Suspicious symptoms and/or signs

● Asymptomatic individuals discovered by routine screening (see "Screening for colorectal

cancer: Strategies in patients at average risk")

● Emergency admission with intestinal obstruction, peritonitis, or rarely, an acute

gastrointestinal (GI) bleed

There are no symptoms in the majority of patients with early stage colon cancer and these
patients are diagnosed as a result of screening. Although the increasing uptake of CRC screening
has led to more cases being diagnosed at an asymptomatic stage, most CRCs (70 to 90 percent
in two contemporary series [6,7]) are diagnosed after the onset of symptoms. Symptoms of CRC
are typically due to growth of the tumor into the lumen or adjacent structures, and as a result,
symptomatic presentation usually reflects relatively advanced CRC. (See "Screening for colorectal
cancer: Strategies in patients at average risk" and "Screening for colorectal cancer in patients with
a family history of colorectal cancer or advanced polyp".)

Symptoms from the local tumor — Typical symptoms/signs associated with CRC include
hematochezia or melena, abdominal pain, otherwise unexplained iron deficiency anemia, and/or a
change in bowel habits [8-13]. Less common presenting symptoms include abdominal distention,
and/or nausea and vomiting, which may be indicators of obstruction. In a retrospective cohort of
over 29,000 patients referred by their general practitioners to an outpatient colorectal surgery
clinic over a 22-year period, presenting symptoms in the 1626 who were eventually diagnosed
with bowel cancer included [14]:

● Change in bowel habits, which was the most common symptom (74 percent)

● Rectal bleeding in combination with change in bowel habits, which was the most common
symptom combination (51 percent of all cancers and 71 percent of those presenting with
rectal bleeding)

● Rectal mass (24.5 percent) or abdominal mass (12.5 percent)

● Iron deficiency anemia (9.6 percent)

● Abdominal pain as a single symptom, which was the least common symptom presentation
(3.8 percent)

In more contemporary series, occult anemia seems more common than a change in bowel habits.
As an example, in a compilation of the most frequent symptoms and findings that prompted
diagnostic colonoscopy in a series of 388 consecutive patients diagnosed with a CRC between
2011 and 2014, the following were noted [6]:

● Blood per rectum (37 percent).

● Abdominal pain (34 percent).
● Anemia (23 percent).
● Six patients (1.9 percent) had incidental colonic hypermetabolic activity detected on a positron
emission tomography/computed tomography (PET/CT) image done for another reason.
● Only four individuals (1.3 percent) underwent diagnostic colonoscopy because of change in
bowel habits (diarrhea).

Obstructive symptoms are more common with cancers that encircle the bowel, producing the so-
called "apple-core" description seen on radiologic imaging (image 1A-B).

Among symptomatic patients, clinical manifestations also differ depending on tumor location:

● A change in bowel habits is a more common presenting symptom for left-sided than right-
sided CRCs. Fecal contents are liquid in the proximal colon and the lumen caliber is larger,
and CRCs are therefore less likely to be associated with obstructive symptoms, including
colicky pain.

● Hematochezia is more often caused by rectosigmoid than right-sided colon cancer.

 ● Iron deficiency anemia from unrecognized blood loss is more common with right-sided CRCs
[15]. Cecal and ascending colon tumors have a fourfold higher mean daily blood loss
(approximately 9 mL/day) than tumors at other colonic sites [16]. (See "Causes and diagnosis
of iron deficiency and iron deficiency anemia in adults", section on 'Search for source of blood
and iron loss'.)

● Abdominal pain can occur with tumors arising at all sites; it can be caused by a partial
obstruction, peritoneal dissemination, or intestinal perforation leading to generalized
peritonitis.

● Rectal cancer can cause tenesmus, rectal pain, and diminished caliber of stools.

Risk of cancer based on symptoms — The risk of CRC posed by particular symptoms has
been addressed in the following studies:

● A meta-analysis of 15 studies concluded that the sensitivity of individual symptoms (change in

bowel habits, anemia, weight loss, diarrhea, abdominal mass) for the diagnosis of CRC was
poor (ranging from 5 to 64 percent) and the specificity was limited, as would be expected for a
low-prevalence disease [17]. However, the specificity was >95 percent for dark-red rectal
bleeding and for the presence of a palpable abdominal mass on examination, indicating that
patients without CRC rarely have these findings and suggesting that the presence of either
makes the diagnosis of a CRC likely.

● The association between constipation and CRC was addressed in a meta-analysis of 28

cross-sectional surveys and cohort studies, which demonstrated no increase in the
prevalence of CRC among individuals with constipation as the primary indication for
colonoscopy [18].

A population-based case-control study of clinical features before the diagnosis of CRC

conducted in 21 primary care practices in Exeter, Devon, in the United Kingdom included 349
patients over the age of 40 who were diagnosed with CRC over a four-year period and 1744
controls without CRC who were matched by age, sex, and general practice [10]. Primary care
records for the two years before diagnosis were reviewed to ascertain symptoms. Of the 349
cases studied, 210 (60 percent) had tumors at or distal to the splenic flexure and 126 (36
percent) were proximal to it, with the remainder having multiple or unknown sites.

Ten features were associated with CRC before diagnosis; in a univariate analysis, the
likelihood ratios for CRC according to symptoms were rectal bleeding 10, weight loss 5.1,
abdominal pain 4.5, diarrhea 3.9, constipation 1.8, abnormal rectal examination 18,
abdominal tenderness 4.6, hemoglobin <10 g/dL 9.5, and positive fecal occult blood 31. The
positive predictive values (PPVs) for abdominal pain, constipation, diarrhea, weight loss, and
rectal bleeding were higher for older patients (70 and over), especially rectal bleeding. When
symptoms were combined, the PPV was highest (>10) for hemoglobin <10 g/dL combined
 with abdominal tenderness. The very high PPV for a positive fecal occult blood test validates
the policy of prompt investigation of patients with positive fecal occult blood tests, particularly
if symptomatic. (See "Tests for screening for colorectal cancer: Stool tests, radiologic imaging
and endoscopy", section on 'Stool-based tests'.)

Given the limitations to timely colonoscopy in many health care settings and the nonspecific
nature of most colorectal (cancer) symptoms, there is emerging interest in using fecal
immunochemical tests for occult blood (iFOBT) using a low threshold of fecal hemoglobin to
maximize sensitivity in order to stratify symptomatic patients who need more urgent
diagnostic colonoscopy. This approach is supported by a limited amount of data showing that
a negative result on iFOBT has a high negative predictive value for ruling out CRC [19].
However, this approach is not in widespread use.

● Another systematic review of 62 studies assessing the relationship between symptoms and
CRC used estimates of sensitivity and specificity to calculate a diagnostic odds ratio (DOR =
[sensitivity/(1-sensitivity)]/[(1-specificity)/specificity]), which provided a single summary
measure of accuracy for each symptom; a high DOR indicates a high correlation between the
symptom and the disease, while a DOR of one means that the symptom presence is no better
than chance in discriminating between diseased and nondiseased patients [20]. The DORs,
sensitivity, likelihood ratio of having the disease if the symptom was present, and likelihood of
having CRC in the absence of the symptom for a variety of symptoms are outlined in the table
(table 1). The authors concluded that only rectal bleeding and weight loss were associated
with the presence of a CRC, and even these had relatively low DORs.

Metastatic disease — Patients may also present with signs/symptoms of metastatic disease.
Approximately 20 percent of patients in the United States have distant metastatic disease at the
time of presentation [3]. CRC can spread by lymphatic and hematogenous dissemination, as well
as by contiguous and transperitoneal routes. The most common metastatic sites are the regional
lymph nodes, liver, lungs, and peritoneum. Patients may present with signs or symptoms referable
to any of these areas. The presence of right upper quadrant pain, abdominal distention, early
satiety, supraclavicular adenopathy, or periumbilical nodules usually signals advanced, often
metastatic disease.

Because the venous drainage of the intestinal tract is via the portal system, the first site of
hematogenous dissemination is usually the liver, followed by the lungs, bone, and many other
sites, including the brain. However, tumors arising in the distal rectum may metastasize initially to
the lungs because the inferior rectal vein drains into the inferior vena cava rather than into the
portal venous system.

Unusual presentations — There are a variety of atypical presentations of CRC. These include:
 ● Local invasion or a contained perforation causing malignant fistula formation into adjacent
organs, such as bladder (resulting in pneumaturia) or small bowel. This is most common with
cecal or sigmoid carcinomas; in the latter case, the condition can mimic diverticulitis.

● Fever of unknown origin, intraabdominal, retroperitoneal, abdominal wall or intrahepatic

abscesses due to a localized perforated colon cancer [21,22]. Streptococcus bovis
bacteremia and Clostridium septicum sepsis are associated with underlying colonic
malignancies in approximately 10 to 25 percent of patients [23]. Rarely, other extraabdominal
infections caused by colonic anaerobic organisms (eg, Bacteroides fragilis) may be
associated with CRC [24]. (See "Infections due to group D streptococci (Streptococcus
bovis/Streptococcus equinus complex)", section on 'Association with colonic neoplasia'.)

● CRC ultimately proves to be the site of origin of approximately 6 percent of adenocarcinomas

of unknown primary sites [25]. (See "Adenocarcinoma of unknown primary site".)

● CRC may be detected on the basis of discovery of liver metastases that are detected
incidentally during studies such as gallbladder or renal ultrasound, or CT scans for evaluation
of other symptoms (eg, dyspnea).

Impact of symptoms on prognosis — The presence of symptoms and their particular type
provide some prognostic importance:

● Patients who are symptomatic at diagnosis typically have more advanced disease and a
worse prognosis [6,26]. In one study of 1071 patients with newly-diagnosed colon cancer, 217
of whom were diagnosed through screening, the patients not diagnosed through screening
were at significantly higher risk for a more invasive tumor (≥T3: relative risk [RR] 1.96), nodal
involvement (RR 1.92), and metastatic disease on presentation (RR 3.37). In addition,
patients not diagnosed through screening had significantly higher death rates (RR 3.02) and
recurrence rates (RR 2.19) as well as shorter survival and disease-free intervals [26]. (See
"Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy".)

● The total number of symptoms may be inversely related to survival for colon but not for rectal
cancer [27]. Whether the duration of symptoms influences prognosis is unclear; the available
data are mixed [28-30].

● Obstruction and/or perforation, although uncommon, carry a poor prognosis, independent of

stage [9,31-34]. Among patients with node-negative colon cancer, obstruction or perforation
are poor prognostic factors that may influence the decision to pursue adjuvant chemotherapy.
(See "Adjuvant chemotherapy for resected stage II colon cancer", section on
'Clinicopathologic variables'.)

● Tumors presenting with rectal bleeding (more commonly those involving the distal colon and
rectum and at an earlier stage than proximal tumors) have a better prognosis [35,36].
 However, bleeding is not an independent predictor of outcome [32,37].

Other determinants of prognosis, including clinicopathologic and molecular features, are

discussed elsewhere. (See "Pathology and prognostic determinants of colorectal cancer".)

DIAGNOSIS

Colorectal cancer (CRC) may be suspected from one or more of the symptoms and signs
described above or may be asymptomatic and discovered by routine screening of average- and
high-risk subjects. Once a CRC is suspected, the next test can be a colonoscopy, barium enema,
or computed tomography colonography. However, examination of tissue is required to establish
the diagnosis; this is usually accomplished by colonoscopy. (See "Screening for colorectal cancer:
Strategies in patients at average risk" and "Screening for colorectal cancer in patients with a family
history of colorectal cancer or advanced polyp" and "Lynch syndrome (hereditary nonpolyposis
colorectal cancer): Cancer screening and management" and "Familial adenomatous polyposis:
Screening and management of patients and families" and "Juvenile polyposis syndrome".)

Histopathologically, the majority of cancers arising in the colon and rectum are adenocarcinomas.
The histologic diagnosis of CRC is discussed in detail elsewhere. (See "Pathology and prognostic
determinants of colorectal cancer", section on 'Histology'.)

Colonoscopy — Colonoscopy is the most accurate and versatile diagnostic test for CRC, since it
can localize and biopsy lesions throughout the large bowel, detect synchronous neoplasms, and
remove polyps. Synchronous CRCs, defined as two or more distinct primary tumors diagnosed
within six months of an initial CRC, separated by normal bowel, and not due to direct extension or
metastasis, occur in 3 to 5 percent of patients [38-40]. The incidence is somewhat lower
(approximately 2.5 percent) when patients with Lynch syndrome are excluded; the presence of
synchronous cancers should raise the clinical suspicion for Lynch Syndrome or MUTYH-
associated polyposis [41,42]. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer):
Clinical manifestations and diagnosis", section on 'Colonic manifestations'.)

The preparation for, diagnostic use of, and complications associated with colonoscopy are
discussed elsewhere. (See "Overview of colonoscopy in adults".)

When viewed through the endoscope, the vast majority of colon and rectal cancers are
endoluminal masses that arise from the mucosa and protrude into the lumen (figure 1). The
masses may be exophytic or polypoid. Bleeding (oozing or frank bleeding) may be seen with
lesions that are friable, necrotic, or ulcerated (picture 1A-B). Circumferential or near-
circumferential involvement of the bowel wall correlates with the so-called "apple-core" description
seen on radiologic imaging (image 1A-B).
A minority of neoplastic lesions in the gastrointestinal tract (both in asymptomatic and
symptomatic individuals) are nonpolypoid and relatively flat or depressed. In one study,
nonpolypoid colorectal neoplasms had a greater association with carcinoma than did polypoid
neoplasms [43]. Cancers that arise from nonpolypoid (flat) adenomas may be more difficult to
visualize colonoscopically than polypoid lesions, but colonoscopy has superior sensitivity in this
situation than does barium enema or computed tomography (CT) colonography.

For endoscopically visible lesions, methods for tissue sampling include biopsies, brushings, and
polypectomy. For lesions that are completely removed endoscopically (with polypectomy,
endoscopic mucosal resection, or endoscopic submucosal dissection), tattooing is important for
subsequent localization if an invasive neoplasm is found, and additional local therapy is needed.
Tattoos are typically placed adjacent to or a few centimeters distal to the lesion, with the location
being documented in the colonoscopy report. Large, laterally spreading colonic polyps can now be
safely removed endoscopically, provided they meet endoscopic criteria that predict their benign
nature (table 2). (See "Endoscopic removal of large colon polyps", section on 'Patient selection'.)

Among asymptomatic patients, colonoscopic miss rates for CRCs in the hands of experienced
operators range from 2 to 6 percent, and missed cancers are most frequently on the right side of
the colon [44-47].

The available data concerning miss rates for CRC among symptomatic patients undergoing
colonoscopy are as follows:

● In a randomized trial comparing colonoscopy versus CT colonography for individuals with

symptoms suggestive of CRC conducted by SIGGAR (Special Interest Group in
Gastrointestinal and Abdominal Radiology) investigators, none of the 55 cancers that were
diagnosed in the cohort of 1072 patients who were randomly assigned to colonoscopy were
missed [48].

● In a systematic review and meta-analysis of 25 diagnostic studies providing data on 9223

patients with a cumulative CRC prevalence of 3.6 percent (414 cancers), the sensitivity of
optical colonoscopy for detection of CRC was 94.7 percent (178 of 188, 95% CI 90-97.2) [49].
Thus, the miss rate was 5.3 percent.

● Large retrospective studies from Canada [50-52] and the United States [53-55] have used
administrative databases to identify patients diagnosed with CRC who had had a colonoscopy
performed for any indication 6 to 60 months prior to CRC diagnosis. These interval, missed,
or post-colonoscopy CRCs accounted for 6 to 9 percent of all CRCs in their series. Other
studies of post-colonoscopy CRC (sometimes called interval cancers) have shown a close
inverse relationship between the incidence of these cancers in a colonoscopist's practice and
that colonoscopist's adenoma detection rate. (See "Overview of colonoscopy in adults",
section on 'Quality indicators'.)
If a malignant obstruction precludes a full colonoscopy preoperatively, the entire residual colon
should be examined soon after resection.

In the absence of an obstruction, where colonoscopy is incomplete, additional options include CT

colonography or Pill Cam colon 2, a wireless colon video endoscopy capsule approved for CRC
screening, although its use in patients with symptoms suggestive of CRC (eg, anemia, rectal
bleeding, weight loss) is controversial. (See 'CT colonography' below and 'PILLCAM 2' below and
"Tests for screening for colorectal cancer: Stool tests, radiologic imaging and endoscopy", section
on 'Capsule endoscopy' and "Wireless video capsule endoscopy", section on 'Colon capsule
endoscopy' and "Overview of computed tomographic colonography".)

As noted above, given the limitations to timely colonoscopy in many health care settings and the
nonspecific nature of most colorectal (cancer) symptoms, there is emerging interest in using fecal
immunochemical tests for occult blood (iFOBT) using a low threshold of fecal hemoglobin to
maximize sensitivity in order to stratify symptomatic patients who need more urgent diagnostic
colonoscopy. This approach is supported by a limited amount of data showing that a negative
result on iFOBT has a high negative predictive value for ruling out CRC [19]. However, this
approach is not in widespread use. (See 'Risk of cancer based on symptoms' above.)

Flexible sigmoidoscopy — Over the last 50 years, a gradual shift toward right-sided or proximal
colon cancers has been observed both in the United States and internationally, with the greatest
increase in incidence in cecal primaries (picture 2). Because of this, and because of the high
frequency of synchronous CRCs, flexible sigmoidoscopy is generally not considered to be an
adequate diagnostic study for a patient suspected of having a CRC, unless a palpable mass is felt
in the rectum. In such cases, a full colonoscopy will still be needed to evaluate the remainder of
the colon for synchronous polyps and cancers (see "Colorectal cancer: Epidemiology, risk factors,
and protective factors", section on 'Incidence'). Nevertheless, screening for CRC using a flexible
sigmoidoscope is one of the few modalities that have been proven through randomized controlled
trials to reduce CRC mortality and incidence [48].

CT colonography — CT colonography (also called virtual colonoscopy or CT colography)

provides a computer-simulated endoluminal perspective of the air-filled distended colon. The
technique uses conventional spiral or helical CT scan or magnetic resonance images acquired as
an uninterrupted volume of data, and employs sophisticated postprocessing software to generate
images that allow the operator to fly-through and navigate a cleansed colon in any chosen
direction. CT colonography requires a mechanical bowel prep that is similar to that needed for
barium enema, since stool can simulate polyps. (See "Overview of computed tomographic
colonography".)

CT colonography has been evaluated in patients with incomplete colonoscopy and as an initial
diagnostic test in patients with symptoms suggestive of CRC.
 Incomplete colonoscopy — Non-completion rates for diagnostic colonoscopy in symptomatic
patients are approximately 11 to 12 percent [48,56]. Reasons for incompleteness include the
inability of the colonoscope to reach the tumor or to visualize the mucosa proximal to the tumor for
technical reasons (eg, partially or completely obstructing cancer, tortuous colon, poor preparation)
and patient intolerance of the examination. In this setting, CT colonography is useful for the
detection of CRC and can provide a radiographic diagnosis, although it can overcall stool as
masses in poorly distended or poorly prepared colons; it also lacks the capability for biopsy or
removal of polyps [49,57-60].

CT colonography should be restricted to patients who are able to pass flatus and capable of
tolerating the oral preparation. For clinically obstructed patients, a gastrointestinal (GI) protocol
abdominal CT scan is a good alternative to CT colonography.

Initial diagnostic test — Systematic reviews of screening studies conducted in asymptomatic

patients suggest that both CT colonography and colonoscopy have similar diagnostic yield for
detecting CRC and large polyps. Comparison of the benefits and costs of the two procedures
depends on other factors, one of the most important of which is the need for additional
investigation after CT colonography and the exposure to radiation, which is particularly important
where recurrent scanning over time may be contemplated such as in screening. (See "Radiation-
related risks of imaging".)

Abnormal results with CT colonography should be followed up by colonoscopy for excision and
tissue diagnosis, or for smaller lesions, additional surveillance with CT colonography. There is
controversy as to the threshold size of a polyp that would indicate the need for (interventional)
colonoscopy and polypectomy. CT colonography also has the ability to detect extracolonic lesions,
which might explain symptoms and provide information as to the tumor stage, but also could
generate anxiety and cost for unnecessary investigation and may have a low yield of clinically
important pathology [61]. (See "Tests for screening for colorectal cancer: Stool tests, radiologic
imaging and endoscopy".)

The performance of diagnostic CT colonography as compared with colonoscopy in patients with

symptoms suggestive of CRC has been addressed in the following studies:

● A systematic review and meta-analysis included 49 studies (11,551 patients) in which patients
underwent CT colonography for the diagnosis of colorectal polyps and cancer with
subsequent colonoscopy for verification of the findings; 43 studies (6668 patients) examined a
symptomatic or disease-enriched population [49]. There were 394 cancers in the symptomatic
population (prevalence 6 percent) and a total of 414 cancers in the entire cohort. CT
colonography detected 96.1 percent of the histologically proven cancers (95% CI 93.9-97.7
percent). In a subset of 25 studies (9223 patients) in which the sensitivity of colonoscopy
could be assessed independently (ie, when the colonoscopy was performed without
knowledge of the prior CT colonography result, an analysis which included predominantly
 data from asymptomatic individuals), the sensitivity of colonoscopy was 94.7 percent (178 of
188 cancers, 95% CI 90.4-97.2 percent).

● The diagnostic performance of CT colonography was directly compared with colonoscopy in

the SIGGAR trial in which 1610 patients with symptoms suggestive of CRC were randomly
assigned to colonoscopy (n = 1072) or CT colonography (n = 538) [48]. The primary endpoint
was the rate of additional colonic investigation after the primary procedure for detection of
CRC or large (>10 mm) polyps. Detection rates for CRC and large polyps were 11 percent for
both procedures. CT colonography missed 1 of 29 CRCs and colonoscopy missed none of
55. However, patients undergoing CT colonography were more than three times more likely to
get additional colonic investigations (30 versus 8 percent). Only one-third of the patients who
underwent additional investigations were found to have CRC or a large polyp.

At least one previously unknown extracolonic finding was reported in 60 percent of the 475
patients who had CT colonography and no diagnosis of CRC. Most were judged to be
clinically unimportant. Among the 48 patients who were investigated further for extracolonic
findings, only approximately one-third received a diagnosis that explained at least one of their
presenting symptoms and only nine patients were found to have an extracolonic malignancy.

Overall, CT colonography had superior patient acceptability compared with colonoscopy in

the short term (immediately after the test) but the benefits of colonoscopy (being more
satisfied with how results were received and less likely to require follow-up colonic
investigations) became apparent after longer-term follow-up (three months) [62].

The available data suggest that CT colonography provides a similarly sensitive, less invasive
alternative to colonoscopy in patients presenting with symptoms suggestive of CRC. However,
given that colonoscopy permits removal/biopsy of the lesion and any synchronous cancers or
polyps that are seen during the same procedure, in our view, colonoscopy remains the gold
standard for investigation of symptoms suggestive of CRC. CT colonography is preferred over
barium enema where access to colonoscopy is limited.

PILLCAM 2 — A colon capsule for CRC screening has been approved by the European
Medicines Agency (EMA) in Europe and by the US Food and Drug Administration. In the United
States, it is approved for use in patients who have had an incomplete colonoscopy. While its role
in screening for CRC is still uncertain, it could be considered in a patient with an incomplete
colonoscopy who lacks obstruction.

Laboratory tests — Although CRC is often associated with iron deficiency anemia, its absence
does not reliably exclude the disease. There is no diagnostic role for other routine laboratory test,
including liver function tests, which lack sensitivity for detection of liver metastases.

Tumor markers — A variety of serum markers have been associated with CRC, particularly
carcinoembryonic antigen (CEA). However, all these markers, including CEA, have a low
diagnostic ability to detect primary CRC due to significant overlap with benign disease and low
sensitivity for early-stage disease [63-66]. A meta-analysis concluded that the pooled sensitivity of
CEA for diagnosis of CRC was only 46 percent (95% CI 0.45-0.47) [67]. No other conventional
tumor marker had a higher diagnostic sensitivity, including carbohydrate antigen 19-9 (CA 19-9,
pooled sensitivity 0.30, 95% CI 0.28-0.32).

Furthermore, specificity of CEA is also limited. In the previously mentioned meta-analysis, the
specificity of CEA for diagnosis of CRC was 89 percent (95% CI 0.88-0.92). Non-cancer-related
causes of an elevated CEA include gastritis, peptic ulcer disease, diverticulitis, liver disease,
chronic obstructive pulmonary disease, diabetes, and any acute or chronic inflammatory state. In
addition, CEA levels are significantly higher in cigarette smokers than in non-smokers [68,69].

An expert panel on tumor markers in breast and colorectal cancer convened by the American
Society of Clinical Oncology (ASCO) recommended that neither serum CEA nor any other marker,
including CA 19-9, should be used as a screening or diagnostic test for CRC [64]. A similar
recommendation has been made by the European Group on Tumor Markers [70].

However, CEA levels do have value in the follow-up of patients with diagnosed CRC. ASCO
guidelines recommend that serum CEA levels be obtained preoperatively in most patients with
demonstrated CRC to aid in surgical treatment planning, posttreatment follow-up, and in the
assessment of prognosis [64]:

● Serum levels of CEA have prognostic utility in patients with newly diagnosed CRC. Patients
with preoperative serum CEA >5 ng/mL have a worse prognosis, stage for stage, than those
with lower levels, although at least some data suggest that elevated preoperative CEA that
normalizes after resection is not an indicator of poor prognosis [71]. (See "Pathology and
prognostic determinants of colorectal cancer", section on 'Preoperative serum CEA'.)

● Elevated preoperative CEA levels that do not normalize following surgical resection imply the
presence of persistent disease and the need for further evaluation. (See "Surveillance after
colorectal cancer resection", section on 'Carcinoembryonic antigen'.)

Furthermore serial assay of postoperative CEA levels should be performed for five years for
patients with stage II and III disease if they may be a potential candidate for surgery or
chemotherapy if metastatic disease is discovered. A rising CEA level after surgical resection
implies recurrent disease and should prompt follow-up radiologic imaging. (See "Surveillance after
colorectal cancer resection".)

Blood-based tests for early detection of CRC, or to monitor for postoperative recurrence, are
under active development at present. Amongst the contenders are Sept9 [72], the Gemini test
[73,74], and blood-based microRNAs [75]
DIFFERENTIAL DIAGNOSIS

The signs and symptoms associated with colorectal cancer (CRC) are nonspecific, and the
differential diagnosis, particularly among patients presenting with of abdominal pain and rectal
bleeding, is broad. (See "Causes of abdominal pain in adults" and "Etiology of lower
gastrointestinal bleeding in adults" and "Evaluation of occult gastrointestinal bleeding" and
"Approach to acute lower gastrointestinal bleeding in adults".)

Many conditions cause signs or symptoms that are similar to colorectal adenocarcinomas
including other malignancies as well as benign lesions such as hemorrhoids, diverticulitis,
infection, or inflammatory bowel disease.

The differential diagnosis of a colonic mass as seen on radiographic or endoscopic studies

includes a number of benign and malignant disorders, the differentiation of which can generally
requires biopsy and histologic evaluation (table 3). In particular, rare malignancies other than
adenocarcinomas that are primary to the large bowel include Kaposi sarcoma (KS), lymphomas,
carcinoid (well-differentiated neuroendocrine) tumors, and metastases from other primary cancers.
(See "Pathology and prognostic determinants of colorectal cancer", section on 'Histology'.)

● Disseminated KS can involve the colon, particularly in patients with AIDS, manifested as
characteristic violaceous macules or nodules [76]. (See "AIDS-related Kaposi sarcoma:
Clinical manifestations and diagnosis", section on 'Gastrointestinal tract'.)

● Primary non-Hodgkin lymphoma of the large bowel most commonly arises in the cecum, right
colon, or rectum and usually presents at an advanced stage in adults. Colonic lymphoma
typically appears as a large solitary mass, although multiple polypoid lesions or diffuse
involvement can occur [77]. (See "Clinical presentation and diagnosis of primary
gastrointestinal lymphomas".)

● Colonic carcinoid tumors are found most commonly in the appendix, rectum, and cecum, and
they tend to develop at a younger age than adenocarcinomas of the colon. Appendiceal and
rectal carcinoids, most of which are less than 2 cm, appear as submucosal nodules and tend
to be indolent. In contrast, primary colonic carcinoid tumors can present as large apple-core
lesions, which can be clinically aggressive and may metastasize. (See "Clinical characteristics
of well-differentiated neuroendocrine (carcinoid) tumors arising in the tubular digestive tract,
lung, and genitourinary tract".)

● Metastases from other primary cancers, most often ovarian cancer, can mimic a primary large
bowel malignancy. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum:
Clinical features and diagnosis", section on 'Differential diagnosis'.)
STAGING

Once the diagnosis of colorectal cancer (CRC) is established, the local and distant extent of
disease is determined to provide a framework for discussing therapy and prognosis. A review of
the biopsy specimen is important prior to making a decision about the need for clinical staging
studies and surgical resection, especially for a cancerous polyp. Polyps with an area of invasive
malignancy that have been completely removed and lack associated adverse histologic features
(positive margin, poor differentiation, lymphovascular invasion) have a low risk of lymphatic and
distant metastases; in such patients, polypectomy alone may be adequate. This is more easily
determined if the polyp is pedunculated. (See "Overview of colon polyps".)

TNM staging system — The tumor, node, metastasis (TNM) staging system of the combined
American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) is the
preferred staging system for CRC. Use of the older Astler-Coller modification of the Duke's
classification is discouraged.

The most recent (eighth edition, 2017) revision of the TNM staging classification contains few
changes compared with the earlier 2010 seventh edition (table 4) [78]. The M1c stage has been
introduced to reflect peritoneal carcinomatosis as a poor prognostic factor, and nodal
micrometastases (tumor clusters >0.2 mm in diameter) are now scored as positive given the
results of a meta-analysis demonstrating a poor prognosis in these patients [79]. (See "Pathology
and prognostic determinants of colorectal cancer", section on 'Nodal micrometastases'.)

In addition, the definition of tumor deposits as they apply to regional nodal status is clarified. This
version also acknowledges the following factors, which are important to consider when making
decisions about treatment but are not yet incorporated into the formal staging criteria:

● Preoperative serum carcinoembryonic antigen (CEA) levels. (See 'Tumor markers' above.)

● Tumor regression score, which reflects the pathologic response to preoperative radiotherapy,
chemoradiotherapy, or chemotherapy (table 5) and the status of the circumferential resection
margin for rectal cancers. (See "Neoadjuvant chemoradiotherapy, radiotherapy, and
chemotherapy for rectal adenocarcinoma", section on 'Prognosis and extent of tumor
regression' and "Pathology and prognostic determinants of colorectal cancer", section on
'Circumferential (radial) margin'.)

● Lymphovascular and perineural invasion. (See "Pathology and prognostic determinants of

colorectal cancer", section on 'Lymphovascular invasion' and "Pathology and prognostic
determinants of colorectal cancer", section on 'Perineural invasion'.)

● Microsatellite instability, which reflects deficiency of mismatch repair enzymes and is both a
prognostic factor and predictive of a lack of response to fluoropyrimidine therapy. (See
 "Pathology and prognostic determinants of colorectal cancer", section on 'Mismatch repair
deficiency'.)

● Mutation status of KRAS, NRAS, and BRAF, because mutations in these genes are
associated with lack of response to agents targeting the epidermal growth factor receptor
(EGFR). (See "Pathology and prognostic determinants of colorectal cancer", section on 'RAS
and BRAF'.)

However, this TNM staging classification is not used in all countries. As examples, in some areas
of the Netherlands, the fifth edition of the TNM staging classification is still used purposely for
rectal cancer, as later modifications were not considered to represent an improvement, whereas in
Japan, none of the revised criteria on satellite deposits that lack evidence of a residual lymph
node were adopted in the most current seventh (2006) edition of the National Cancer Staging
Manual edited by the Japanese Society for Cancer of the Colon and Rectum because of the lack
of sufficient justification for this change [80].

Radiographic, endoscopic (including biopsy), and intraoperative findings can be used to assign a
clinical stage, while assessment of the pathologic stage (termed pT, pN, pM) requires histologic
examination of the resection specimen. Preoperative radiation and chemotherapy (as are often
undertaken for locally advanced rectal cancer) can significantly alter clinical staging; as a result,
posttherapy pathologic staging is designated with a yp prefix (ie, ypT, ypN). (See "Pathology and
prognostic determinants of colorectal cancer", section on 'Posttherapy staging for rectal cancer'.)

Clinical staging evaluation — Preoperative clinical staging is best accomplished by physical

examination (with particular attention to ascites, hepatomegaly, and lymphadenopathy, and
potential fixation of rectal cancers), computed tomography (CT) scan of the abdomen and pelvis,
and chest imaging. Although frequently obtained preoperatively, liver enzymes may be normal in
the setting of small hepatic metastases and are not a reliable marker for exclusion of liver
involvement (picture 3). The single most common liver test abnormality associated with liver
metastases is an elevation in the serum alkaline phosphatase level [81].

CT scan — In the United States and elsewhere, the standard practice at most institutions is
that all patients with stage II, III, or IV CRC undergo chest, abdomen, and pelvic CT, either prior to
or following resection, an approach endorsed by the National Comprehensive Cancer Network
[82]. In general, it is preferable to obtain these scans prior to, rather than after surgery, as the scan
results will occasionally change surgical planning.

Abdomen and pelvis — In patients with newly-diagnosed CRC, preoperative abdominal

and pelvic CT scans can demonstrate regional tumor extension, regional lymphatic and distant
metastases, and tumor-related complications (eg, obstruction, perforation, fistula formation)
[83,84]. The sensitivity of CT for detecting distant metastasis is higher (75 to 87 percent) than for
detecting nodal involvement (45 to 73 percent) or the depth of transmural invasion (approximately
50 percent) [83,85-90]. The sensitivity of CT for detection of malignant lymph nodes is higher for
rectal than for colon cancers; perirectal adenopathy is presumed to be malignant since benign
adenopathy is typically not seen in this area in the absence of demonstrable inflammatory process
(eg, proctitis, fistula, perirectal abscess) [91].

CT scan is not a reliable diagnostic test for low-volume tumor on peritoneal surfaces [92]. The
sensitivity of CT for detecting peritoneal implants depends on the location and size of the implants.
In one study, the sensitivity of CT for nodules <0.5 cm was 11 percent and it was only 37 percent
for implants 0.5 to 5 cm [93].

Although commonly obtained, the necessity of preoperative abdominal/pelvic CT for all patients
with CRC is debated. In a retrospective review of 180 resected patients, only 3 of 67 patients had
incidental findings on CT that altered the surgical approach [88]. Assessment of hepatic
metastases by intraoperative ultrasound and manual palpation of the liver may provide a better
yield than preoperative CT, particularly for patients who are found to have transmural involvement
(T3/4) at the time of exploration [94-96]. However, the increasing use of laparoscopic colonic
resections precludes manual palpation, and even with open procedures surgeons may not have
adequate access to the liver depending upon the location of the incision and the extent of
adhesions from prior surgery.

The finding of liver metastases on preoperative studies may not necessarily alter the surgical
approach to the primary tumor, particularly in patients who are symptomatic from their primary
tumor (eg, bleeding, impending obstruction). In patients with four or fewer hepatic lesions,
resection may be curative, with five-year relapse-free survival rates of 24 to 38 percent. Although
most surgeons advocate resection of the primary tumor and synchronous hepatic metastases at
two different operations, some approach both sites at the same time. (See "Management of
potentially resectable colorectal cancer liver metastases".)

Chest — The clinical benefit of routine clinical staging with chest CT is also controversial. At
least in theory, imaging of the chest might be of more value for rectal cancer since venous
drainage of the lower rectum is through the hemorrhoidal veins to the vena cava, bypassing the
liver, and lung metastases might be more common [97].

The major issue is the frequent finding of indeterminate lesions (10 to 30 percent), which add to
the clinical complexity (ie, should further preoperative diagnostic workup be undertaken) but are
seldom malignant (7 to 20 percent). A systematic review of 12 studies including 5873 patients
undergoing staging for a newly diagnosed CRC [98] found that 732 (9 percent) had indeterminate
pulmonary nodules on preoperative chest CT. Of these, 80 (11 percent) turned out to be colorectal
metastases at follow-up. Generally, the presence of regional nodal metastases at the time of
resection, multiple numbers of indeterminate pulmonary nodules, size ≥5 mm, rectal as compared
with colon cancer, parenchymal versus subpleural location of the nodule, and distant metastases
elsewhere were significantly associated with malignancy, while calcification was associated with a
benign etiology. Overall, the risk of malignancy for most patients with indeterminate pulmonary
nodules (approximately 1 percent) seems sufficiently low that further preoperative diagnostic
workup is unnecessary.

Liver MRI — Contrast-enhanced magnetic resonance imaging (MRI) of the liver can identify
more hepatic lesions than are visualized by CT, and is particularly valuable in patients with
background fatty liver changes [99]. A meta-analysis concluded that MRI is the preferred first-line
imaging study for evaluating CRC liver metastases in patients who have not previously undergone
therapy [100]. However, newer-generation CT scanners and the use of triple-phase imaging during
contrast administration has improved sensitivity of CT for detection of liver metastases. In current
practice, liver MRI is generally reserved for patients who have suspicious but not definitive findings
on CT scan, particularly if better definition of hepatic disease burden is needed in order to make
decisions about potential hepatic resection. (See "Management of potentially resectable colorectal
cancer liver metastases", section on 'Patient selection'.)

PET scans — Positron emission tomography (PET) scans with or without integrated CT
(PET/CT) do not appear to add significant information to CT scans for routine preoperative staging
of CRC [101-103]. The established role of PET scanning in patients with CRC as an adjunct to
other imaging modalities is described in the following settings:

● Localizing site(s) of disease recurrence in patients who have a rising serum CEA level and
nondiagnostic conventional imaging evaluation following primary treatment. In this setting,
PET scanning can potentially localize occult disease, permitting the selection of patients who
may benefit from exploratory laparotomy [104-107]. (See "Surveillance after colorectal cancer
resection".)

In an illustrative series, 105 such patients underwent PET scanning and subsequent
abdominopelvic CT scans [104]. Compared with CT and other conventional diagnostic
studies, PET scanning had a higher sensitivity (87 versus 66 percent) and specificity (68
versus 59 percent) for the detection of clinically relevant tumor. In a second report, PET scan
findings led to a potentially curative resection in 14 of 50 patients (28 percent) with elevated
serum CEA levels and a completely normal or equivocal conventional diagnostic work-up
[105].

● Evaluation of patients who are thought to be present or future candidates for resection of
isolated CRC liver metastases. The routine use of PET prior to attempted resection reduces
the number of nontherapeutic laparotomies.

An important point is that recent chemotherapy may alter the sensitivity of PET for the
detection of colorectal liver metastases, an effect thought related to decreased cellular
metabolic activity of the tumor. However, generally, the benefit of a PET scan is to detect
extrahepatic metastases in patients considered liver resection candidates, and in this
 situation, it is appropriate to obtain a PET prior to initiation of chemotherapy. This subject is
addressed in detail elsewhere. (See "Management of potentially resectable colorectal cancer
liver metastases", section on 'Utility of PET scans'.)

Locoregional staging for rectal cancer — An accurate determination of tumor location within
the rectum and disease extent is necessary prior to treatment in order to select the surgical
approach and to identify those patients who are candidates for initial chemoradiotherapy prior to
surgery. (See "Neoadjuvant chemoradiotherapy, radiotherapy, and chemotherapy for rectal
adenocarcinoma", section on 'Selecting patients for neoadjuvant treatment'.)

Digital rectal examination (DRE), rigid sigmoidoscopy, transrectal ultrasound, transrectal

endoscopic ultrasound, and pelvic MRI can all assist in determining the need for radical resection
versus local excision, and whether the patient is a candidate for preoperative therapy. This subject
is discussed elsewhere. (See "Pretreatment local staging evaluation for rectal cancer".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Colorectal cancer".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topics (see "Patient education: Colon and rectal cancer (The Basics)")

● Beyond the Basics topics (see "Patient education: Colon and rectal cancer (Beyond the
Basics)" and "Patient education: Colorectal cancer treatment; metastatic cancer (Beyond the
Basics)")

SUMMARY
● Patients with colorectal cancer (CRC) may present in three ways (see 'Clinical presentation'
above):

• Patients with suspicious symptoms and/or signs

• Asymptomatic individuals discovered by routine screening (see "Screening for colorectal

cancer: Strategies in patients at average risk")

• Emergency admission with intestinal obstruction, peritonitis, or rarely, an acute

gastrointestinal (GI) bleed

● Although the increasing uptake of CRC screening has led to more cases being diagnosed at
an asymptomatic stage, most CRCs are diagnosed after the onset of symptoms (most
commonly rectal bleeding, abdominal pain, otherwise unexplained iron deficiency anemia
and/or a change in bowel habits). A change in bowel habits is a more common presenting
symptom for left-sided as compared with right-sided cancers. Hematochezia is more likely
with rectal than colon cancers, and occult colonic bleeding is more common with cecal and
ascending colon cancers. (See 'Symptoms from the local tumor' above.)

One in five patients with CRC presents with metastatic disease. The most common metastatic
sites are the regional lymph nodes, liver, lungs, and peritoneum. (See 'Metastatic disease'
above.)

Unusual presentations of CRC include malignant fistula formation, fever of unknown origin,
sepsis from Streptococcus bovis and Clostridium septicum, and adenocarcinoma of unknown
primary. (See 'Unusual presentations' above.)

● A positive fecal occult blood test has a much higher predictive value for CRC than any single
or combination of symptoms, warranting high priority for colonoscopic follow-up. (See
'Differential diagnosis' above.)

● The vast majority of colon and rectal cancers are endoluminal adenocarcinomas that arise
from the mucosa. Colonoscopy is the most versatile diagnostic test in symptomatic individuals
(see 'Colonoscopy' above). Computed tomography (CT) colonography provides a similarly
sensitive, less invasive alternative to colonoscopy in patients presenting with symptoms
suggestive of CRC. However, given that colonoscopy permits removal/biopsy of the lesion
and any synchronous cancers or polyps that are seen during the same procedure,
colonoscopy remains the gold standard for investigation of symptoms suggestive of CRC. CT
colonography is preferred over barium enema where access to colonoscopy is limited. (See
'Initial diagnostic test' above.)

In patients in whom for technical reasons the tumor cannot be reached by colonoscopy (eg,
partially obstructing cancer, tortuous colon, poor prep) or because of patient intolerance, CT
colonography can provide a radiographic diagnosis.
 ● Once the diagnosis is established, the local and distant extent of disease spread is
determined to provide a framework for discussing therapy and prognosis. Preoperative clinical
staging is best accomplished by physical examination, CT scan of the abdomen and pelvis,
and chest imaging. (See 'Clinical staging evaluation' above.)

Positron emission tomography (PET) scans do not appear to add significant information to CT
scans for routine preoperative staging of a newly-diagnosed CRC except for the evaluation of
patients who are thought to be candidates for resection of isolated CRC liver metastases.
(See 'PET scans' above.)

● Additional procedures (digital rectal examination [DRE], rigid sigmoidoscopy, transrectal

endoscopic ultrasound, and/or magnetic resonance imaging [MRI]) are indicated for
locoregional staging of patients with rectal cancer to select the surgical approach and to
identify those patients who are candidates for initial radiotherapy or chemoradiotherapy rather
than surgery. (See 'Locoregional staging for rectal cancer' above.)

● There is no diagnostic role for routine laboratory testing in screening or staging CRC.
However, serum carcinoembryonic antigen (CEA) levels should be obtained preoperatively
and postoperatively in patients with demonstrated CRC to aid surgical treatment planning and
assessment of prognosis. (See 'Tumor markers' above.)

ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge Dennis J Ahnen, MD, who contributed to
an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 2496 Version 68.0

GRAPHICS

Rectal cancer as seen on barium enema

Double-contrast barium enema shows an eccentric mass arising from the

anterior wall of the rectum (arrow).

Courtesy of Jonathan Kruskal, MD, PhD.

Graphic 82202 Version 3.0

Cancer of the colon as seen on barium enema

Double contrast barium enema shows an apple-core lesion surrounding the

lumen of the descending colon.

Courtesy of Jonathan Kruskal, MD.

Graphic 75818 Version 3.0

Symptoms associated with colorectal cancer

DOR* 1-
Sensitivity LR+ LR–
Symptom (95% AUC ¶ specificity
(95% CI) (95% CI) (95% CI)
CI*) (95% CI)

Rectal 2.6 0.66 0.46 0.25 1.9 0.7

bleeding Δ (1.9-3.6) (0.38-0.55) (0.19-0.31) (1.5-2.3) (0.6-0.8)
p<0.001

Blood mixed 3.1 0.68 0.49 0.24 2.1 0.7

with stool (2.0-4.8) (0.30-0.69) (0.13-0.40) (1.5-2.8) (0.5-0.9)
p<0.001

Blood: dark 3.9 0.71 0.29 0.10 3.1 0.8

red (1.7-9.2) (0.09-0.65) (0.03-0.28) (1.6-6.0) (0.6-1.1)
p = 0.004

Change in 1.5 0.57 0.32 0.24 1.4 0.9

bowel habit (0.8-2.8) (0.21-0.46) (0.15-0.35) (0.9-2.1) (0.7-1.1)
p = 0.16

Constipation 1.1 0.52 0.12 0.11 1.1 1.0

(0.8-1.5) (0.08-0.18) (0.07-0.16) (0.8-1.5) (1.0-1.0)
p = 0.48

Diarrhea 0.9 0.47 0.15 0.17 0.9 1.0

(0.4-1.7) (0.07-0.28) (0.09-0.29) (0.5-1.6) (0.9-1.1)
p = 0.65

Abdominal 0.7 0.45 0.19 0.24 0.8 1.1

pain (0.5-1.1) (0.13-0.28) (0.17-0.33) (0.6-1.1) (1.0-1.2)
p = 0.12

Weight loss 2.9 0.67 0.20 0.08 2.5 0.9

(1.6-5.0) (0.12-0.31) (0.05-0.13) (1.5-4.0) (0.8-1.0)
p = 0.001

LR+: the likelihood ratio of having colorectal cancer in the presence of the symptom; LR–: the likelihood ratio of having
colorectal cancer in the absence of the symptom.
* DOR: diagnostic odds ratio. No association between symptom and cancer if DOR = 1.
¶ AUC: Area Under the receiver operating characteristic Curve. No association between symptom and cancer if AUC = 0.5.
Δ Bleeding of any type.

Reproduced from: Adelstein B, Macaskill P, Chan SF, et al. Most bowel cancer symptoms do not indicate colorectal cancer
and polyps: a systematic review. BMC Gastroenterology 2011; 11:65. Copyright © 2011 Adelstein et al.

Graphic 88734 Version 4.0

Colon cancer seen on CT scan and colonoscopy

(A) Computed tomographic (CT) scan showing a filling defect in the ascending colon (red
arrow) along with an involved lymph node (yellow arrow).
(B) Colon cancer identified in the ascending colon on subsequent colonoscopy.

Graphic 83618 Version 1.0

Adenocarcinoma of the colon

Adenocarcinoma of the colon may have a variety of appearances on endoscopy. Panel A: a typical
exophytic mass; Panel B: a friable polypoid mass; Panel C: circumferential adenocarcinoma.

Courtesy of James B McGee, MD.

Graphic 74346 Version 1.0

Normal sigmoid colon

Endoscopic appearance of the normal sigmoid colonic mucosa. The fine

vasculature is easily visible, and the surface is shiny and smooth. The folds
are of normal thickness.

Courtesy of James B McGee, MD.

Graphic 55563 Version 1.0

Necrotic adenocarcinoma of the colon

Endoscopy showing necrotic colonic lesions that usually suggest an advanced

stage of malignancy. Panel A: severe tissue destruction has led to necrosis and
bleeding; Panel B: the longstanding tumor has extended deeply into the mucosa
and become necrotic.

Courtesy of James B McGee, MD.

Graphic 54234 Version 1.0

Endoscopic criteria suggesting malignancy of a polyp

Firm consistency

Adherence

Ulceration

Friability

Graphic 68868 Version 1.0

Familial colon cancer

These images are from a 38-year-old man who was found to have heme positive
stool. His father and two uncles died of colon cancer before the age of fifty.
Panel A: The initial study was a barium enema (although a colonoscopy is more
commonly used as the initial diagnostic study for heme positive stools). The
barium enema reveals a filling defect in the cecum (arrow). Panels B and C: A
CT scan of the abdomen shows a large exophytic mass (colored in pink in panel
C) involving the cecum (arrows). Panel D: Colonoscopy reveals that the large
exophytic lesion occupies most of the cecum. Adenocarcinoma was confirmed by
biopsy. Despite the size of the lesion, the tumor had not spread beyond the
colonic wall.

Courtesy of James B McGee, MD.

Graphic 51584 Version 2.0

Causes of a colonic mass

Malignant lesions
Adenocarcinoma

Lymphoma

Carcinoid tumor

Kaposi sarcoma

Prostate cancer

Benign lesions
Crohn colitis

Diverticulitis

Endometriosis

Solitary rectal ulcer

Lipoma

Tuberculosis

Amebiasis

Cytomegalovirus

Fungal infection

Nematode (roundworm) infection

Extrinsic lesion

Graphic 66850 Version 4.0

Colorectal cancer TNM staging AJCC UICC 8th edition

Primary tumor (T)

T category T criteria

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no

extension through muscularis mucosae)

T1 Tumor invades the submucosa (through the muscularis mucosa but not into the
muscularis propria)

T2 Tumor invades the muscularis propria

T3 Tumor invades through the muscularis propria into pericolorectal tissues

T4 Tumor invades* the visceral peritoneum or invades or adheres ¶ to adjacent organ or

structure

T4a Tumor invades* through the visceral peritoneum (including gross perforation of the
bowel through tumor and continuous invasion of tumor through areas of inflammation
to the surface of the visceral peritoneum)

T4b Tumor directly invades* or adheres ¶ to adjacent organs or structures

* Direct invasion in T4 includes invasion of other organs or other segments of the colorectum as a result of direct
extension through the serosa, as confirmed on microscopic examination (for example, invasion of the sigmoid
colon by a carcinoma of the cecum) or, for cancers in a retroperitoneal or subperitoneal location, direct invasion
of other organs or structures by virtue of extension beyond the muscularis propria (ie, respectively, a tumor on
the posterior wall of the descending colon invading the left kidney or lateral abdominal wall; or a mid or distal
rectal cancer with invasion of prostate, seminal vesicles, cervix, or vagina).
¶ Tumor that is adherent to other organs or structures, grossly, is classified cT4b. However, if no tumor is present
in the adhesion, microscopically, the classification should be pT1-4a depending on the anatomical depth of wall
invasion. The V and L classification should be used to identify the presence or absence of vascular or lymphatic
invasion whereas the PN prognostic factor should be used for perineural invasion.

Regional lymph nodes (N)

N category N criteria

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 One to three regional lymph nodes are positive (tumor in lymph nodes measuring
≥0.2 mm), or any number of tumor deposits are present and all identifiable lymph
nodes are negative

N1a One regional lymph node is positive

N1b Two or three regional lymph nodes are positive

N1c No regional lymph nodes are positive, but there are tumor deposits in the:
Subserosa
Mesentery
Nonperitonealized pericolic, or perirectal/mesorectal tissues

N2 Four or more regional nodes are positive

N2a Four to six regional lymph nodes are positive

N2b Seven or more regional lymph nodes are positive

Distant metastasis (M)

M category M criteria

M0 No distant metastasis by imaging, etc; no evidence of tumor in distant sites or

organs. (This category is not assigned by pathologists.)

M1 Metastasis to one or more distant sites or organs or peritoneal metastasis is identified

M1a Metastasis to one site or organ is identified without peritoneal metastasis

 M1b Metastasis to two or more sites or organs is identified without peritoneal metastasis

M1c Metastasis to the peritoneal surface is identified alone or with other site or organ
metastases

Prognostic stage groups

When T is... And N is... And M is... Then the stage group
is...

Tis N0 M0 0

T1, T2 N0 M0 I

T3 N0 M0 IIA

T4a N0 M0 IIB

T4b N0 M0 IIC

T1-T2 N1/N1c M0 IIIA

T1 N2a M0 IIIA

T3-T4a N1/N1c M0 IIIB

T2-T3 N2a M0 IIIB

T1-T2 N2b M0 IIIB

T4a N2a M0 IIIC

T3-T4a N2b M0 IIIC

T4b N1-N2 M0 IIIC

Any T Any N M1a IVA

Any T Any N M1b IVB

Any T Any N M1c IVC

TNM: tumor, node, metastasis; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control.

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the
AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing. Corrected at 4th
printing, 2018.

Graphic 111438 Version 6.0

Modified Ryan scheme for tumor regression scoring in rectal cancer treated
preoperatively

Tumor regression
Description
score

No viable cancer cells (complete response) 0

Single cells or rare small groups of cancer cells (near-complete response) 1

Residual cancer with evident tumor regression, but more than single cells or rare small 2
groups of cancer cells (partial response)

Extensive residual cancer with no evident tumor regression (poor or no response) 3

Modified from: Ryan R, Gibbons D, Hyland JM, et al. Pathological response following long-course neoadjuvant
chemoradiotherapy for locally advanced rectal cancer. Histopathology 2005; 47:141.
http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1365-2559.2005.02176.x/abstract. Copyright © 2005. Reproduced
with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is
needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions
department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission'
link accompanying this article on Wiley Online Library (http://onlinelibrary.wiley.com).

Graphic 111439 Version 1.0

Metastatic colon cancer

Multiple liver metastases seen during laparotomy in a patient with colon cancer.

Courtesy of Richard B Freeman, Jr, MD.

Graphic 81255 Version 1.0